Aluminium lithium hydride → 3-(4-Bromophenyl)-3-methylazetidine

HRID 1022434Notes

Reaction equation

HRID 1022434 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:22]#[N:23])([CH3:21])[CH2:9]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH3:9])[CH2:21][NH:23][CH2:22]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86704562Toluene-4-sulfonic acid 2-(4-bromo-phenyl)-2-cyano-2-methyl-ethyl ester

Product 1

HCID 794606093-(4-Bromophenyl)-3-methylazetidineYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of toluene-4-sulfonic acid 2-(4-bromo-phenyl)-2-cyano-2-methyl-ethyl ester (10 g, 25.38 mmol) in dry tetrahydrofuran (100 mL) was added 1M lithium aluminum hydride (25.3 mL diluted with 25.3 mL of dry tetrahydrofuran) via syringe pump at −10° C. for 1 h and stirring was continued for 30 min at 10° C. The reaction mixture was quenched with water (1 mL), diluted with tetrahydrofuran (3 mL) followed by a 15% aqueous sodium hydroxide solution (1 mL) and water (3 mL), and filtered through a Celite® pad. The filtrate was concentrated in vacuo. Flash chromatography (8% methanol/methylene chloride) afforded 3-(4-bromo-phenyl)-3-methyl-azetidine as an off-white solid (4.0 g, 70%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.52 (s, 3H) 2.42-2.57 (m, 1H) 3.40 (d, J=7.34 Hz, 2H) 3.72 (d, J=7.34 Hz, 2H) 7.15 (d, J=8.80 Hz, 2H) 7.39-7.61 (m, 2H). LC-MS calcd. for C10H12BrN [M+] 226, obsd. 226.0/228.2.

Workup

  1. customThe reaction mixture was quenched with water (1 mL)
  2. additiondiluted with tetrahydrofuran (3 mL)
  3. filtrationfiltered through a Celite® pad
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-2be5b3a421694b33aa20460a33866412
Source dataset
uspto-grants-2014_05
Patent number
US08722661B2

Reaction notes

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